Mass spectrometry (MS) is an analytical technique that allows the determination of the m/z of ions of sample molecules. Generally, mass spectrometry involves ionizing sample molecule(s) and analyzing the ions in a mass analyzer. One exemplary MS technique known in the art is Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. FT-ICR mass spectrometry has received considerable attention for its ability to make accurate, high resolution mass measurements.
FIG. 1 demonstrates the general structure of one FT-ICR mass spectrometer system 100 known in the art. FT-ICR mass spectrometer system 100 includes an ion source 110, a first mass analyzer 120, and an FT-ICR unit 140. In operation, the first mass analyzer 120 (e.g., linear quadrupole electrodes 122 to which RF and/or DC voltages can be applied) receives ions from the ion source 110 and filters those ions (e.g., selectively transmits ions of a selected m/z range) to the downstream elements to be further analyzed.
In known systems, the FT-ICR unit 140 generally comprises a magnetic ion trap (e.g., a Penning trap) having a ring electrode 142 and two end-cap electrodes 144a,b. A Penning trap is a device used to store charged particles. A Penning trap generally stores charged particles using a homogeneous magnetic field and an inhomogeneous quadrupole electric field. The end-cap electrodes 144a,b include orifices 146 disposed on the central, longitudinal axis (A) of the MS system 100 through which ions are received from the ion source 110/first mass analyzer 140 and through which the ions are transmitted to downstream elements (e.g., mass analyzer 160), respectively. In order to trap the charged particles, FT-ICR units like that shown in FIG. 1 generally utilize a static electric field generated between the end-cap electrodes 144a,b (typically maintained at a DC voltage of the same polarity as the ions to be trapped) and the ring electrode 142 (typically maintained at a DC voltage of the opposite polarity as the ions to be trapped) to confine the ions axially (i.e., in the z-direction along the central axis (A) between the orifices 146 of the end-cap electrodes 144a,b). Additionally, a static, uniform magnetic field (B, typically not less than 1 T) is applied along the direction in which ions are injected (i.e., along the central axis (A)) so as to confine the charged particles radially (i.e., in the x- and y-directions, perpendicular to the axis of the magnetic field).
Because the resolution capability of FT-ICR is generally related to the uniformity and intensity of the magnetic field to which the ions are subjected (e.g., certain performance features vary as a function of the square of the intensity of the magnetic field such that a minimum value of about 1 T is recommended in high performance MS applications), magnetic ion traps for FT-ICR have traditionally utilized strong electromagnets or super-conducting electromagnets (e.g., solenoid 148, within which the ring electrode 142 and end-cap electrodes 144a,b are housed) to produce the high-intensity magnetic fields (e.g., at least 1 T, sometimes as high as 7-15 Tesla) along the central axis (A), as schematically depicted in FIG. 1 by the arrow indicating the direction of the magnetic field (B). Such electromagnets, however, can be extremely expensive and cumbersome (e.g., heavy, bulky), and require complex power supplies and/or cooling installations for operation. The high cost and limited mobility of FT-ICR systems resulting from the size of the magnets (electromagnets or permanent) has heretofore limited the adoption of FT-ICR despite the technique's potential benefits (e.g., high accuracy and resolution).
U.S. Provisional Application No. 62/085,459 (hereinafter the “'459 Application”), entitled “Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, is directed to a new FT-ICR system or mass spectrometer. This new system uses a new side-on injection Penning trap. This trap uses smaller, less expensive permanent magnets (as well as electromagnets) to reduce the cost, size, and/or complexity of the trap relative to conventional Penning traps. This trap also uses electrodes printed on printed circuit boards (PCBs) to reduce the cost, size, and/or complexity of the trap.
This new side-on injection Penning trap enables Fourier transform ion cyclotron resonance mass spectrometry to be performed in a relatively narrow gap and allows ions to be injected into the trap in a direction substantially perpendicular to the magnetic fields applied to the gap. As a result, smaller, less expensive magnets can be used to produce the high-intensity, uniform magnetic fields utilized in high performance FT-ICR/MS applications.
FIG. 2 is an exemplary schematic diagram of a side-on injection FT-ICR system 200. Side-on injection FT-ICR system 200 includes an ion source 210 for generating ions from a sample of interest, an ion guide 220 for focusing and/or filtering the ions to be transmitted thereby, a side-on injection Penning trap 240, and a downstream mass analyzer 260 (as an option). The exemplary side-on injection Penning trap 240 includes a plurality of electrodes 242, 244 for generating an electric field within the side-on injection Penning trap 240 and at least one magnet 248 for generating a magnetic field between the electrodes 242, 244 such that the ions can be trapped via the combination of the effects thereon of the electric and magnetic fields.
In various aspects, ions generated by the ion source 210 can be injected into the side-on injection Penning trap 240 substantially along the central axis (A). After being transmitted into the side-on injection Penning trap 240 and into the space bounded by the electrodes 242, 244 disposed on opposed sides of the central axis (A), the ions are subjected to the magnetic and electric fields generated therein via the magnet(s) 248 and the electrodes 242, 244. As schematically depicted in FIG. 2, for example, the magnet(s) 248 can be configured to generate a magnetic field (B) within the side-on injection Penning trap 240 having a magnetic field axis that is substantially perpendicular to the injection axis/central axis (A).
The at least one magnet 248 can have a variety of configurations for generating a magnetic field within the side-on injection Penning trap 240. By way of non-limiting example, the at least one magnet 248 can be one or more permanent magnets (i.e., an object made from magnetized material that creates its own magnetic field) or an electromagnet (e.g., a solenoid that generates a magnetic field when an electric current flows therethrough) that are configured to generate a uniform, high-intensity magnetic field within the gap between the electrodes 242, 244 in a direction substantially perpendicular to the injection axis. The electrodes 242, 244 can also have a variety of configurations such that various electric potentials can be applied thereto so as to change the electric field within the side-on injection Penning trap 240, thereby altering the amplitude of ions' cyclotron motion and/or the trajectory of the ions' drift.
FIG. 3 is an exemplary schematic diagram of an electrode 242 of the side-on injection FT-ICR system 200 of FIG. 2. An exemplary SIMION simulation is depicted in FIG. 3, demonstrating the path 310 of a cation (positive ion) during its injection from the ion guide 220 of FIG. 2 into the magnetic trap 240 of FIG. 2, during which the depicted exemplary potentials of FIG. 3 are applied to the electrodes 242a-e of FIG. 3 (SIMION is an ion motion simulator in vacuum provided by Scientific Instrument Service, Inc. NJ). The electrodes 242a-e are formed on a PCB, for example.
As indicated by arrow 320 of Figure, the cation is injected into the gap between the electrodes 242, 244 of FIG. 2 substantially along the central axis of the ion guide 220. Upon entering the side-on injection Penning trap 240 of FIG. 2, the ion is subject to the electric field generated by the electrodes 242, 244 of FIG. 2 and the uniform magnetic field generated in the gap between the electrodes. As demonstrated schematically and understood by a person skilled in the art, the cation would tend to move along an equipotential line of superimposed electrical potential gradient within the uniform magnetic field generated by the magnets 248 of FIG. 2, with the cation's cyclotron motion overlapping on the transverse motion (drift).
Accordingly, upon entering the side-on injection Penning trap 240 of FIG. 2, the cation proceeds initially along the non-conducting portion between the upper arch electrodes 242d,b of FIG. 3 (−1V) and the lower arch electrodes 242e,c of FIG. 3 (+1V). At the intersection of the upper, inner arch electrode 242b (−1V), the lower, inner arch electrode 242c (+1V), and the center electrode 242a (−1V), however, the ion is deflected from its initial axis along equipotential lines around the center electrode 242a (−1V) and the lower, inner arch electrode 242c (+1V). As such, the cation travels substantially along the non-conductive portion between the center electrode 242a (−1V) and the lower, inner arch electrode 242c (+1V). At the intersection of the lower, inner arch electrode 242c (+1V), the center electrode 242a (−1V), and the upper, inner arch electrode 242b (−1V), the cation is again deflected along the non-conductive portion extending between the lower, inner arch electrode 242c (+1V) and the upper, inner arch electrode (−1V), and is ejected along the non-conductive portion on the left side of FIG. 3. As such, under the exemplary conditions depicted in FIG. 3, the cation can be transmitted through the magnetic ion trap (e.g., into downstream mass analyzer of FIG. 2), the ejection from the magnetic ion trap again occurring substantially along the central axis (A) of FIG. 2. It should be appreciated that the arrangement of the electrodes 242a-e and the potentials applied thereto in FIG. 3 are merely exemplary, and can be modified in order to otherwise control the motion of the ions. By way of example, if the polarity of the electrodes 242a-e of FIG. 3 were reversed, it would be appreciated that an anion (negative) injected into this modified trap would exhibit substantially the same path through the magnetic ion trap as that depicted for the cation in FIG. 3. Line F-F′ shows the location of cross-section shown in FIG. 4.
Ion Instability
Ions have a drift motion when they are in a DC potential gradient (electric field) coupled with a uniform magnetic field as shown in FIG. 2. In a general model to discuss this drift motion, the DC potential gradient is often uniform, (Φ=const*x or (Ex=−const, Ey=0, Ex=0), for example. In the Penning trap of FIG. 2, however, because the DC field is produced using two PCBs facing each other with a narrow gap, the DC field is not uniform.
FIG. 4 is a cross-sectional side view 400 of the electrodes of FIG. 2. The location of the cross-section with respect to electrode 242 of FIG. 3 is shown in FIG. 3 as line F-F′. FIG. 4 shows that the DC field between the electrodes of FIG. 2 is not uniform. This non-uniform potential makes a focusing region and a defocusing region based on the direction of the magnetic field. For positively charge ions, the positively biased pad side is focusing, and the negatively biased pat side is defocusing. Arrows 410 show that the negatively biased electrodes are defocusing for positive ions and arrows 420 show that the positively biased electrodes are focusing for positive ions.
As described above, ions are injected to follow the non-conducting portions or paths of the electrodes 242 and 244 of FIG. 2. For example, as shown in FIG. 3 ions are injected at location 320 along an axis to follow the non-conducting path between electrodes 242d and 242e. However, as FIG. 4 shows these non-conducting paths between positively and negatively biased electrodes produce non-uniform DC fields in the gaps between electrodes. These non-uniform fields, in turn, produce focusing and defocusing regions.
As a result, if ions are directed along the non-conducting paths between positively and negatively biased electrodes, at least a portion of the ions are in the defocusing region. Ions in the defocusing region become unstable and are lost from the trap. For example, FIG. 4 shows that positive ions following the non-conducting portion between pads 242a and 242c and between pads 244a and 244c that are closer to the negatively biased pads 242a and 244a feel the force shown by arrows 410 and are defocused away from the center of the gap and lost from the trap. In contrast, positive ions following the non-conducting portion between pads 242a and 242c and between pads 244a and 244c that are closer to the positively biased pads 242c and 244c feel the force shown by arrows 420 and are focused to the center of the gap and stabilized in the trap.
The at least partial ion instability produced by non-uniform DC fields in the gap of the trap results in a reduced ion efficiency of the trap (or reduced number of ions in the trap). As a result, systems and methods are needed to inject ions into the trap so that the ions are maintained in the focusing region of the non-uniform DC fields produced by the pad electrodes of the side-on Penning trap. In other words, if an ion is traveling in the focusing area, the ion should have an efficient transmission, but if an ion is traveling in the defocusing area, the ion can be lost during injection. The issue then is how to control the ion trajectory to keep them in the focusing region.
Lorentz Force at the Entrance of the Trap in Continuous Flow
FIG. 5 is an exemplary plot 500 showing how the magnetic field varies across a side-on Penning trap. FIG. 5 shows that the magnetic field within the trap is constant or uniform. However, outside of the trap, the magnetic field quickly decreases in intensity. Therefore, FIG. 5 shows that ions entering the trap experience a sharply increasing magnetic field as they move toward the trap.
The Lorentz force is a force that a moving charged particle experiences as a result of the combined effects of an electric field and a magnetic field. The Lorentz force, F, is expressed as F=q[E+(v×B)], where q is the charge of the charged particle, E is the electric field experienced by the charged particle, v is the velocity of the charged particle, and B is the magnetic field experienced by the charged particle.
The increasing magnetic field that ions experience as they are injected into a side-on Penning trap with a certain velocity produces a Lorentz force. This Lorentz force can cause the ions to be deflected away from the trap, preventing ion injection. As a result, systems and methods are needed to compensate for the Lorentz force that is produced when ions are injected into a side-on Penning trap.
Large m/z Range
In a side-on Penning trap, long term ion accumulation or trapping is accomplished by capturing ions in pulses or pulse-wise. There are, therefore, two modes of operation. There is an injection mode and a trapping mode. During the injection mode, injected ions are located in the arc of a trapping orbit. FIG. 3, for example, shows the injected ions in the arc of a trapping orbit during the injection mode. In the trapping mode, the DC voltages applied to the electrodes are switched to trap the ions in a complete circle between the electrodes.
The duration of the injection mode is dependent on the strength of magnetic field and the DC bias of electrodes. The duration is, for example, 10-50 micro seconds. Another way of expressing the duration is as a drift frequency. The drift frequency is typically given by V/(2Bd2). V is a bias difference between the center circle and the first ring, B is the magnetic field intensity, and d is the distance between two PCB plates. This frequency is an analog of the magnetron motion frequency in a conventional FT-ICR cell.
An important feature of the side-on Penning trap, therefore, is that the trapping duration or drift frequency is not dependent on an injected ion's m/z values and injection kinetic energy. The only dependence on m/z value or injection kinetic energy is in the cyclotron motion. This is the spiral or circular motion of the ions. In other words, the path shape of ions in a side-on FT-ICR system is dependent on m/z value and injection kinetic energy, but the path length of the ions is not dependent on m/z value or injection kinetic energy.
The fact that the path length of the ions is not dependent on m/z value or injection kinetic energy means that a side-on FT-ICR system can potentially analyze a collection of ions with a large range of m/z values at the same time. The primary problem is getting the ions with a large range of m/z values into the side-on Penning trap. For example, if ions with a large range of m/z values are injected from a continuous flow device, the continuous flow device will separate the ions by m/z value before they reach the side-on Penning trap. As a result, systems and methods are needed to inject a collection of ions with a large range of m/z values into the side-on Penning trap at the same time.